Chapter 7
Bone Tissue
• Tissues and organs of
the skeletal system
• Histology of osseous
tissue
• Bone development
• Physiology of osseous
tissue
• Bone disorders
Bone as a Tissue
• Dynamic tissue that continually remodels itself
• Bones and bone tissue
– bone or osseous tissue is a connective tissue with a
matrix hardened by minerals
(calcium phosphate)
– bones make up the skeletal system
• individual bones are made up of bone
tissue, marrow, cartilage & periosteum
• Functions of the skeletal system
– support, protection, movement, blood formation,
mineral reservoir, pH balance & detoxification
Shapes of Bones
Structure of a Flat Bone
• External and internal
surfaces of flat bone
are composed of
compact bone
• Middle layer is
spongy bone (diploe).
No marrow cavity
• Blow to the skull
may fracture outer
layer and crush
diploe, but not harm
inner compact bone
Structure of a Long Bone
• Periosteum &
articular
cartilage
• Compact &
spongy bone
• Endosteum
• Yellow marrow
General Features of Bones
• Shaft (diaphysis) is cylinder of compact bone containing
marrow cavity (medullary cavity) & lined with endosteum
(layer of osteopenic cells and reticular connective tissue)
• Enlarged ends (epiphyses) are spongy bone covered with a
layer of compact bone
– enlarged to strengthen joint & provide for attachment of tendons
and ligaments
• Joint surface covered with articular cartilage (lubrication)
• Remainder of bone covered with periosteum
– outer fibrous layer of collagen fibers continuous with tendons or
perforating(Sharpey’s) fibers that penetrate into bone matrix
– inner osteogenic layer important for growth & healing
• Epiphyseal plate or line depends on age
Cells of Osseous Tissue (1)
• Osteogenic cells reside in endosteum, periosteum or central canals
– arise from embryonic fibroblasts and become only source for new osteoblasts
– multiply continuously & differentiate into amitotic osteoblasts in response to
stress or fractures
• Osteoblasts form and help mineralize organic matter of matrix
• Osteocytes are osteoblasts that have become trapped in the matrix
they formed
– cells in lacunae connected by gap junctions inside canaliculi
– signal osteoclasts & osteoblasts about mechanical stresses
Cells of Osseous Tissue (2)
• Osteoclasts develop in bone marrow by the fusion of 3-50 of the
same stem cells that give rise to monocytes found in blood
• Reside in pits called resorption bays that they have eaten into the
surface of the bone
Matrix of Osseous Tissue
• Dry weight is 1/3 organic & 2/3 inorganic matter
• Organic matter
– collagen, glycosaminoglycans, proteoglycans & glycoproteins
• Inorganic matter
– 85% hydroxyapatite (crystallized calcium phosphate salt)
– 10% calcium carbonate
– other minerals (fluoride, sulfate, potassium, magnesium)
• Combination provides for strength & resilience
– minerals resist compression; collagen resists tension
– fiberglass = glass fibers embedded in a polymer
– bone adapts to tension and compression by varying proportions
of minerals and collagen fibers
Compact Bone
• Osteon (haversian system) = basic structural unit
– cylinders of tissue formed from layers (lamellae) of
matrix arranged around central canal holding a blood
vessel
• collagen fibers alternate between right- and left-handed
helices from lamella to lamella
– osteocytes connected to each other and their blood
supply by tiny cell processes in canaliculi
• Perforating canals or Volkmann canals
– vascular canals perpendicularly joining central canals
• Circumferential or outer lamellae
Histology of Compact Bone
Blood Vessels of Compact Bone
Spongy Bone
• Spongelike appearance formed by rods and
plates of bone called trabeculae
– spaces filled with red bone marrow
• Trabeculae have few osteons or central canals
– no osteocyte is far from blood of bone marrow
• Provides strength with little weight
– trabeculae develop along bone’s lines of stress
Spongy Bone Structure and Stress
Bone Marrow
• Soft tissue that occupies the medullary
cavity of a long bone or the spaces amid
the trabeculae of spongy bone
• Red marrow looks like thick blood
– mesh of reticular fibers and immature cells
– hemopoietic means produces blood cells
– found in vertebrae, ribs, sternum, pelvic
girdle and proximal heads of femur and
humerus in adults
• Yellow marrow
– fatty marrow of long bones in adults
• Gelatinous marrow of old age
– yellow marrow replaced with reddish jelly
Intramembranous Ossification
• Produces flat bones of skull & clavicle
• Steps of the process
– mesenchyme condenses into a sheet of soft tissue
• transforms into a network of soft trabeculae
– osteoblasts gather on the trabeculae to form osteoid
tissue (uncalcified bone)
– calcium phosphate is deposited in the matrix
transforming the osteoblasts into osteocytes
– osteoclasts remodel the center to contain marrow
spaces & osteoblasts remodel the surface to form
compact bone
– mesenchyme at the surface gives rise to periosteum
Intramembranous Ossification
Endochondral Ossification
• Primary ossification center forms in cartilage model
– chondrocytes near the center swell to form primary
ossification center
– matrix is reduced & model becomes weak at that point
– cells of the perichondrium produce a bony collar
– cuts off diffusion of nutrients and hastens their death
• Primary marrow space formed by periosteal bud
– osteogenic cells invade & transform into osteoblasts
– osteoid tissue deposited and calcified into trabeculae at
same time osteoclasts work to enlarge the primary
marrow cavity
Primary Ossification Center & Marrow Space
• Both form in center of cartilage model -- same process
begins again subsequently at ends of cartilage model.
The Metaphysis
• Transitional zone between head and shaft of a
developing long bone
• Zone of reserve cartilage is layer of resting cartilage
• Zone of cell proliferation is layer
– chondrocytes multiply forming columns of flat lacunae
• Zone of cell hypertrophy shows hypertrophy
• Zone of calcification shows mineralization between
columns of lacunae
• Zone of bone deposition -- chondrocytes die and
each channel is filled with osteoblasts and blood
vessels to form a haversian canal & osteon
The Metaphysis
Secondary Ossification Center
• Begin to form in the epiphyses near time of birth
• Same stages occur as in primary ossification center
– result is center of epiphyseal cartilage being transformed
into spongy bone
• Hyaline cartilage remains on joint surface as
articular cartilage and at junction of diaphysis &
epiphysis (epiphyseal plate)
– each side of epiphyseal plate has a metaphysis
Metaphysis & Secondary Ossification Center
• Metaphysis is cartilagenous material that remains as growth
plate between medullary cavity & secondary ossification
centers in the epiphyses.
The Fetal Skeleton at 12 Weeks
Epiphyseal Plates
Bone Growth and Remodeling
• Grow and remodel themselves throughout life
– growing brain or starting to walk
– athletes or history of manual labor have greater density & mass
of bone
• Cartilage grows by both appositional & interstitial growth
• Bones increase in length by interstitial growth of
epiphyseal plate
• Bones increase in width by appositional growth
– osteoblasts lay down matrix in layers parallel to the outer surface
& osteoclasts dissolve bone on inner surface
– if one process outpaces the other, bone deformities occur
(osteitis deformans)
Achondroplastic Dwarfism
• Short stature but normalsized head and trunk
– long bones of the limbs
stop growing in childhood
but other bones unaffected
• Result of spontaneous
mutation when DNA is
replicated
– mutant allele is dominant
• Pituitary dwarf has lack
of growth hormone
– short stature with normal
proportions
Mineral Deposition
• Mineralization is crystallization process in which
ions (calcium, phosphate & others) are removed
from blood plasma & deposited in bone tissue
• Steps of the mineralization process
– osteoblasts produce collagen fibers that spiral along the
length of the osteon in alternating directions
– fibers become encrusted with minerals hardening matrix
• ion concentration must reach the solubility product for crystal
formation to occur & then positive feedback forms more
• Ectopic ossification is abnormal calcification
– may occur in lungs, brain, eyes, muscles, tendons or
arteries (arteriosclerosis)
Mineral Resorption
• Process of dissolving bone & releasing minerals
into the blood
– performed by osteoclasts “ruffled border”
• hydrogen pumps in the cell membrane secrete hydrogen
ions into the space between the osteoclast & the bone
• chloride ions follow by electrical attraction
• hydrochloric acid with a pH of 4 dissolves bone minerals
• an enzyme (acid phosphatase) digests the collagen
• Dental braces reposition teeth, creating greater
pressure on the bone on one side of the tooth and
less on the other side
– increased pressure stimulates osteoclasts; decreased
pressure stimulates osteoblasts to remodel jaw bone
Functions of Calcium & Phosphate
• Phosphate is a component of DNA, RNA, ATP,
phospholipids, & acid-base buffers
• Calcium is needed for communication between
neurons, muscle contraction, blood clotting &
exocytosis
• Calcium plasma concentration is 9.2 to 10.4
mg/dL -- 45% is as Ca+2, rest is bound to plasma
proteins & is not physiologically active
• Phosphate plasma concentration is 3.5 to 4.0
mg/dL & occurs in 2 forms: HPO4 -2 & H2PO4-
Ion Imbalances
• Changes in phosphate concentration have little effect
• Changes in calcium can be serious
– hypocalcemia is deficiency of blood calcium
• causes excessive excitability of nervous system leading to
muscle spasms, tremors or tetany
– laryngospasm may cause suffocation
• calcium normally binds to cell surface contributing to resting membrane
potential
– with less calcium, sodium channels open more easily exciting neuron
– hypercalcemia
• excessive calcium binding to cell surface makes sodium channels less likely
to open, depressing nervous system
• Calcium phosphate homeostasis depends on calcitriol,
calcitonin & PTH
Carpopedal Spasm
• Hypocalcemia causing overexcitability of nervous
system and muscle spasm of hands and feet
Calcitriol (Activated Vitamin D)
• Produced by the following process
– UV radiation penetrating the epidermal keratinocytes converts a
cholesterol derivative (7-dehydrocholesterol) to previtamin D3
and then (cholecalciferol) D3
– liver adds OH to convert it to calcidiol
– kidney adds OH to convert calcidiol to calcitriol
• Calcitriol behaves as a hormone (blood-borne messenger)
– stimulates intestine to absorb calcium, phosphate & magnesium
– weakly promotes urinary reabsorption of calcium ions
– promotes osteoclast activity to raise blood calcium concentration
to the level needed for bone deposition
• Abnormal softness of the bones is called rickets in children
and osteomalacia in adults
Calcitriol Synthesis & Action
Hormonal Control of Calcium Balance
• Calcitriol, PTH and calcitonin maintain normal
blood calcium concentration.
Calcitonin
• Secreted by C cells of the thyroid gland when
calcium concentration rises too high
• Functions
– reduces osteoclast activity by as much as 70% in 15
minutes
– increases the number & activity of osteoblasts
• Important role in children, but little effect in adults
– calcitonin deficiency is not known to cause any disease
in adults
– may be useful in reducing bone loss in osteoporosis
Parathyroid Hormone
• Secreted by the parathyroid glands found on the
posterior surface of the thyroid gland
• Released when calcium blood level is too low
• Functions
– binds to osteoblasts causing them to release osteoclaststimulating factor that stimulates osteoclast multiplication &
activity
– promotes calcium resorption by the kidneys
– promotes calcitriol synthesis in the kidneys
– inhibits collagen synthesis and bone deposition by osteoblasts
• Injection of low levels of PTH can cause bone deposition
Negative Feedback Loops in Calcium
Other Factors Affecting Bone
• 20 or more hormones, vitamins & growth factors
not well understood
• Bone growth especially rapid at puberty
– hormones stimulate proliferation of osteogenic cells
and chondrocytes in growth plate
– adolescent girls grow faster than boys & reach their
full height earlier (estrogen has stronger effect)
– males grow for a longer time
• Growth ceases when epiphyseal plate “closes”
– anabolic steroids may cause premature closure of
growth plate producing short adult stature
Fractures and Their Repair
• Stress fracture is a break caused by abnormal
trauma to a bone
– car accident, fall, athletics, etc
• Pathological fracture is a break in a bone
weakened by some other disease
– bone cancer or osteoporosis
• Fractures are classified by their structural
characteristics -- causing a break in the skin,
breaking into multiple pieces, etc
– or after a physician who first described it
Types of Bone Fractures (Table 7.3)
Healing of Fractures
• Normally healing takes 8 - 12 weeks (longer in
elderly)
• Stages of healing
– fracture hematoma (1)
• broken vessels form a blood clot
– granulation tissue (2)
• fibrous tissue formed by fibroblasts & infiltrated by capillaries
– callus formation (3)
• soft callus of fibrocartilage replaced by hard callus of bone in 6
weeks
– remodeling (4) occurs over next 6 months as spongy
bone is replaced with compact bone
Healing of Fractures
1
2
3
4
Treatment of Fractures
• Closed reduction
– fragments are aligned with manipulation & casted
• Open reduction
– surgical exposure & repair with plates & screws
• Traction is not used in elderly due to risks of long-term
confinement to bed
– hip fractures are pinned & early walking is encouraged
• Electrical stimulation is used on fractures that take
longer than 2 months to heal
• Orthopedics = prevention & correction of injuries and
disorders of the bones, joints & muscles
Fractures and Their Repairs
Osteoporosis
• Most common bone disease
• Bones lose mass & become brittle due to loss of both
organic matrix & minerals
– risk of fracture of hip, wrist & vertebral column
– lead to fatal complications such as pneumonia
– widow’s (dowager’s) hump is deformed spine
• Postmenopausal white women at greatest risk
– by age 70, average loss is 30% of bone mass
• ERT slows bone resorption, but best treatment is
prevention -- exercise & calcium intake (1000 mg/day)
between ages 25 and 40
• Therapies to stimulate bone deposition are still under
investigation
Effects of Osteoporosis